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ASPIRATIONAL EDUCATORS--The nation supports education in Tibet Autonomous Region

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Beijing Review 2020年第37期63卷 32-33页

作者： evan Li 不详

Having worked as a teacher and then schoolmaster for more than a decade,38-year-old Liang Xin,a native of Beijing,made a decision in 2018 that changed the life of a group of Tibetan students and also his own.

关键词： education Tibetan Tibet

Targeting Tyrosyl-DNA phosphodiesterase I to enhance toxicity of phosphodiester linked DNA-adducts

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Cancer Drug Resistance 2019年第4期2卷 1153-1163页

作者： evan J.Brettrager Robert C.A.M.van Waardenburg Department of Pharmacology and Toxicology University of Alabama at BirminghamBirminghamAL 35294-0019USA

Our genomic DNA is under constant assault from endogenous and exogenous sources,which needs to be resolved to maintain cellular *** eukaryotic DNA repair enzyme Tyrosyl-DNA phosphodiesterase I(Tdp1)catalyzes the hydrolysis of phosphodiester bonds that covalently link adducts to ***1 utilizes two catalytic histidines to resolve a growing list of *** DNA-adducts can be divided into two groups:small adducts,including oxidized nucleotides,RNA,and non-canonical nucleoside analogs,and large adducts,such as(drug-stabilized)topoisomerase-DNA covalent complexes or failed Schiff base reactions as occur between PARP1 and *** Tdp1 substrates are generated by chemotherapeutics linking Tdp1 to cancer drug resistance,making a compelling argument to develop small molecules that target Tdp1 as potential novel therapeutic ***1’s unique catalytic cycle,which is centered on the formation of Tdp1-DNA covalent reaction intermediate,allows for two principally different targeting strategies:(1)catalytic inhibition of Tdp1 catalysis to prevent Tdp1-mediated repair of DNA-adducts that enhances the effectivity of chemotherapeutics;and(2)poisoning of Tdp1 by stabilization of the Tdp1-DNA covalent reaction intermediate,which would increase the half-life of a potentially toxic DNA-adduct by preventing its resolution,analogous to topoisomerase targeted poisons such as topotecan or *** catalytic Tdp1 mutant that forms the molecular basis of the autosomal recessive neurodegenerative disease spinocerebellar ataxia with axonal neuropathy best illustrates this concept;however,no small molecules have been reported for this ***,we concisely discuss the development of Tdp1 catalytic inhibitors and their results.

关键词： Tdp1 small molecules DNA topoisomerases Camptothecins oxidative DNA damage DNA adducts Etoposide chain terminating nucleotides/nucleoside analogs DNA metabolism drug development

Molecular basis of cranial suture biology and disease:Osteoblastic and osteoclastic perspectives

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Genes & Diseases 2014年第1期1卷 120-125页

作者： Maureen Beederman evan M.Farina Russell R.Reid Section of Plastic&Reconstructive Surgery Department of SurgeryThe University of Chicago Medical Center5841 South Maryland AvenueMC 6035ChicagoIL 60637USA Pritzker School of Medicine and The Laboratory of Craniofacial BiologyUniversity of Chicago MedicineChicagoIL 60637USA

The normal growth and development of the skull is a tightly regulated process that occurs along the osteogenic interfaces of the cranial ***,the borders of the calvarial bones and neighboring tissues above and below,function as a *** coordinated remodeling efforts of bone deposition and resorption,the cranial sutures maintain a state of patency from infancy through early adulthood as the skull continues to grow and accommodate the developing brain’s demands for ***,when this delicate balance is disturbed,a number of pathologic conditions ensue;and if left uncorrected,may result in visual and neurocognitive impairments.A prime example includes craniosynostosis,or premature fusion of one or more cranial and/or facial suture(s).At the present time,the only therapeutic measure for craniosynostosis is surgical correction by cranial vault ***,elegant studies performed over the past decade have identified several genes critical for the maintenance of suture patency and induction of suture *** deeper understandings of the pathogenesis and molecular mechanisms that regulate suture biology may provide necessary insights toward the development of non-surgical therapeutic alternatives for patients with cranial suture *** this review,we discuss the intricate cellular and molecular interplay that exists within the suture among its three major components:dura mater,osteoblastic related molecular pathways and osteoclastic related molecular pathways.

关键词： Cranial sutures Craniosynostosis Dura mater Osteoblasts Osteoclasts

Mako:A Graph-based Pattern Growth Approach to Detect Complex Structural Variants

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Genomics, Proteomics & Bioinformatics 2022年第1期20卷 205-218页

作者： Jiadong Lin Xiaofei Yang Walter Kosters Tun Xu Yanyan Jia Songbo wang Qihui Zhu Mallory Ryan Li Guo Chengsheng Zhang The Human Genome Structural Variation Consortium Charles Lee Scott E.Devine evan E.Eichler Kai Ye School of Automation Science and Engineering Faculty of Electronic and Information EngineeringXi’an Jiaotong UniversityXi’an 710049China MOE Key Lab for Intelligent Networks&Networks Security Faculty of Electronic and Information EngineeringXi’an Jiaotong UniversityXi’an 710049China Genome Institute the First Affiliated Hospital of Xi’an Jiaotong UniversityXi’an 710061China Leiden Institute of Advanced Computer Science Faculty of ScienceLeiden UniversityLeiden 2311EZNetherland School of Computer Science and Technology Faculty of Electronic and Information EngineeringXi’an Jiaotong UniversityXi’an 710049China The Jackson Laboratory for Genomic Medicine FarmingtonCT 06032USA Precision Medicine Center the First Affiliated Hospital of Xi’an Jiaotong UniversityXi’an 710061China Institute for Genome Sciences University of Maryland School of MedicineBaltimoreMD 21201USA Department of Genome Sciences University of Washington School of MedicineSeattleWA 98119USA Howard Hughes Medical Institute University of WashingtonSeattleWA 98195USA The School of Life Science and Technology Xi’an Jiaotong UniversityXi’an 710049China 不详

Complex structural variants(CSVs) are genomic alterations that have more than two breakpoints and are considered as the simultaneous occurrence of simple structural ***,detecting the compounded mutational signals of CSVs is challenging through a commonly used model-match *** a result,there has been limited progress for CSV discovery compared with simple structural ***,we systematically analyzed the multi-breakpoint connection feature of CSVs,and proposed Mako,utilizing a bottom-up guided model-free strategy,to detect CSVs from paired-end short-read ***,we implemented a graph-based pattern growth approach,where the graph depicts potential breakpoint connections,and pattern growth enables CSV detection without pre-defined *** evaluations on both simulated and real datasets revealed that Mako outperformed other ***,validation rates of CSVs on real data based on experimental and computational validations as well as manual inspections are around 70%,where the medians of experimental and computational breakpoint shift are 13 bp and 26 bp,***,the Mako CSV subgraph effectively characterized the breakpoint connections of a CSV event and uncovered a total of 15 CSV types,including two novel types of adjacent segment swap and tandem dispersed *** analysis of these CSVs also revealed the impact of sequence homology on the formation of *** is publicly available at https://***/xjtu-omics/Mako.

关键词： Next-generation sequencing Complex structural variant Pattern growth Graph mining Formation mechanism

Polymersomes scalably fabricated via flash nano- precipitation are non-toxic in non-human primates and associate with leukocytes in the spleen and kidney following intravenous administration

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Nano Research 2018年第10期11卷 5689-5703页

作者： Sean D. Allen Yu-Gang Liu Sharan Bobbala Lei Cai Peter I. Hecker Ryan Temel evan A. Scott Interdisciplinary Biological Sciences Northwestern University IL 60208 USA Department of Biomedical Engineering Northwestern University IL 60208 USA Saha Cardiovascular Research Center University of Kentucky KY40506 USA Department of Pharmacology and Nutritional Sciences University of Kentucky KY40506 USA

Vesicular nanocarrier formulations confer the ability to deliver hydrophobic and hydrophilic cargos simultaneously to cells of interest in vivo. While liposomal formulations reached the clinic long ago, younger technologies such as polymeric vesicles （polymersomes） have yet to make the transition to clinical approval and use, in part due to difficulties in ensuring their safe and scalable production. In this work, we demonstrate the scalable production of poly（ethylene glycol）-block-poly（propylene sulfide）（PEG-bl-PPS） polymersomes via flash nanoprecipitation, and further show the safe administration of these nanocarriers to mice and non-human primates. In mice, PEG-bl-PPS polymersomes were found to be well tolerated at up to 200 mg/（***）. Following the administration of a more relevant 20 mg/（***） dosage in non-human primates, polymersomes were found to associate with numerous phagocytic immune cell populations, including a remarkable 68% of plasmacytoid dendritic cells and 〉 95% of macrophages in the spleen, while showing no toxicity or abnormalities in the liver, kidney, spleen, or blood. Despite the presence of a dense PEG corona, neither anti-PEG antibodies nor complement activation were detected. This work provides evidence of the translatability of PEG-bI-PPS polymersomes into the clinic for therapeutic applications in humans.

关键词： polymersome non-human primate nanoprecipitation toxicity biodistribution

PRESERVATION AND PROSPERITY--Traditional arts contribute to poverty alleviation in Tibet

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Beijing Review 2020年第37期63卷 24-25页

作者： evan Li 不详

Tsamjo,a former farm worker,is from Tsethang in Tibet Autonomous Region in southwest *** town is known for a traditional art that goes back for centuries,serge ***,durable and static free,the Tsethang serge,a kind of cashmere unique to the area,is considered to be the finest of all Tibetan *** dates back to the Tang Dynasty(618-907)and was used to make the robes of the nobles because of its ornate patterns and elaborate weaving that takes 18 procedures.

关键词： China. southwest Tibetan

Predictive value of SYNTAX score II for clinical outcomes in octogenarian undergoing percutaneous coronary intervention

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Journal of Geriatric Cardiology 2016年第9期13卷 733-739页

作者： evan Kurniawan Feng-Hua DING Qi ZHANG Zhen-Kun YANG Jian HU Wei-Feng SHEN Rui-Yan ZHANG Department of Cardiology Rui Jin Hospital School of Medicine Shanghai Jiao Tong University Shanghai China

Objective To evaluate the predictive value of SYNTAX Score II （SS-II） for percutaneous coronary intervention （PCI） in octogenarian （≥ 80 years old） undergoing PCI. Methods ＆ Results Data from three consecutive years of octogenarian undergoing PCI from Ruijin Hospital （Shanghai, China） was retrospectively collected （n = 308）. Follow up clinical data at one year including all cause mortality, cardiac mortality and main adverse cardiovascular and cerebrovascular events （MACCE） were collected. Patients were stratified according to tertiles of SS-II for PCI： SS-II 〈 26 （n = 104）, SS-II： 27-31 （n = 102）, SS-II 〉 31 （n = 102）. After adjustment for confounding factors, SS-II for PCI was an independent risk factors for all cause mortality （odds ratio： 2.77, 95% CI： 1.13-8.06; P = 0.04）. Kaplan-Meier curves showed higher event rates for all cause mortality and cardiac mortality in higher tertile of SS-II for PCI （Log-Rank test P = 0.002 and P = 0.001, respectively）. SSdl for PCI predicted one year mortality in octogenarian population undergoing PCI. Conclusions In octogenarian, SS-II which incorporated clinical variables with angiographic anatomy variable was suitable in risk stratifying and predicting clinical outcomes at one year.

关键词： Clinical research Elderly Risk stratification

Ketamine use disorder:preclinical,clinical,and neuroimaging evidence to support proposed mechanisms of actions

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Intelligent Medicine 2022年第2期2卷 61-68页

作者： Leah Vines Diana Sotelo Allison Johnson evan Dennis Peter Manza Nora D.Volkow Gene-Jack wang Laboratory of Neuroimaging National Institute on Alcohol Abuse and AlcoholismNational Institutes of Health10 Center DrRm B2L124BethesdaMarylandUnited States

Ketamine,a noncompetitive N-methyl-D-aspartate(NMDA)receptor antagonist,has been exclusively used as an anesthetic in medicine and has led to new insights into the pathophysiology of neuropsychiatric *** studies have shown that low subanesthetic doses of ketamine produce antidepressant effects for individuals with ***,its use as a treatment for psychiatric disorders has been limited due to its reinforcing effects and high potential for diversion and *** studies have focused on understanding the molecular mechanisms underlying ketamine’s antidepressant effects,but a precise mechanism had yet to be *** we review different hypotheses for ketamine’s mechanism of action including the direct inhibition and disinhibition of NMDA receptors,aminomethylphosphonic acid receptors(AMPAR)activation,and heightened activation of monoaminergic *** proposed mechanisms are not mutually exclusive,and their combined influence may exert the observed structural and functional neural *** term use of ketamine induces brain structural,functional impairments,and neurodevelopmental effects in both rodents and *** misuse has increased rapidly in the past 20 years and is one of the most common addictive drugs used in *** proposed mechanisms of action and supporting neuroimaging data allow for the development of tools to identify‘biotypes’of ketamine use disorder(KUD)using machine learning approaches,which could inform intervention and treatment.

关键词： Ketamine Neuroimaging N-methyl-D-aspartate Dopamine Serotonin Glutamatergic Gamma-aminobutyric acid

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From the Editor

Chinese Journal of Applied Linguistics 1998年第2期21卷 3-4页

作者： evan Davies

There are five sections to this issue of Teaching English in China . These reflect some of the important challenges facing ELT in China at present, as well as also coming to bear on the broader issues worldwide. The sections include the process of educational change, the teaching and learning of oral English, intensive and extensive reading, the teaching and learning of vocabulary and a last section containng a range of issues within ELT. Researchers in the field of ELT have relatively recently recognized the importance of educational change as well as its inevitability. In this section of seven articles, some of the stages of the process of education-

关键词： oral From the Editor